Ischemic postconditioning for stroke treatment: current experimental advances and future directions

Ischemic postconditioning (IPostC) protects against brain injury induced by stroke and is a potential strategy for ischemic stroke treatment. Understanding its underlying mechanisms and potential hurdles is essential for clinical translation. In this review article, we will summarize the current advances in IPostC for stroke treatment and the underlying protective mechanisms. Strong evidence suggests that IPostC reduces brain infarct size, attenuates blood-brain barrier (BBB) damage and brain edema, and improves neurological outcomes. IPostC also promotes neurogenesis and angiogenesis at the recovery phase of ischemic stroke. The protective mechanisms involve its effects on anti-oxidative stress, anti-inflammation, and anti-apoptosis. In addition, it regulates neurotransmitter receptors, ion channels, heat shock proteins (HSP) 40/70, as well as growth factors such as BDNF and VEGF. Furthermore, IPostC modulates several cell signaling pathways, including the PI3K/Akt, MAPK, NF-κB, and the Gluk2/PSD95/MLK3/MKK7/JNK3 pathways. We also discuss the potential hurdles for IPostC's clinical translation, including insufficient IPostC algorithm studies, such as therapeutic time windows and ischemia-reperfusion periods and cycles, as well as its long-term protection. In addition, future studies should address confounding factors such as age, sex, and pre-existing conditions such as hypertension and hyperglycemia before stroke onset. At last, the combination of IPostC with other treatments, such as tissue plasminogen activator (t-PA), merits further exploration.